Profiles of Lewisx-containing glycoproteins and glycolipids in sera of patients with adenocarcinoma.
Oligosaccharides with Lex determinant (Gal beta 1----4[Fuc alpha 1----3]GlcNAc) are accumulated in large quantities in various adenocarcinomas. Monoclonal antibodies recognizing mono-, di-, or trimeric Lex showed a preferential staining of specific stages of human fetal tissues and various human adenocarcinomas. Thus, these carbohydrate epitopes are typical of oncodevelopmental antigens. The present study investigated the presence of Lex epitope in sera of normal individuals and cancer patients, utilizing two high-affinity monoclonal antibodies, SH1 and SH2, directed to mono- and dimeric Lex structures, respectively. The Lex antigen in serum was eluted in the void volume fraction of a gel filtration column, determined by using monoclonal antibody SH1, and found to be carried on a glycoprotein with a molecular weight of approximately 200,000. The Lex antigen was present in the void volume fraction of the majority (85%) of sera from adenocarcinoma patients. Although the Lex epitope was also detected in a smaller proportion (33%) of normal sera, its levels were significantly lower than in cancer sera. Lex antigen was also detected in serum glycolipid fraction; however, no significant differences were observed in normal and cancer sera. A double determinant solid phase immunoassay utilizing SH2 as the capture antibody and SH1 as the detecting antibody allowed direct determination of Lex levels in sera. By the use of this direct assay, the levels of serum Lex were found to increase in association with the progression of colorectal cancer (Dukes A to D). The percentage of detectability in sera from colon cancer patients was as follows: Dukes A, 20%; Dukes B, 45%; Dukes C, 67%; and Dukes D, 74%. The levels of serum Lex were also of prognostic value in Dukes C cancer patients after surgery and during postoperative follow-up.
Singhal
A K
AK
Biomembrane Institute, Seattle, Washington.
Orntoft
T F
TF
Nudelman
E
E
Nance
S
S
Schibig
L
L
Stroud
M R
MR
Clausen
H
H
Hakomori
S
S
D000230:Adenocarcinoma / Q000097:blood* / Q000276:immunology; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000032:analysis*; D003110:Colonic Neoplasms / Q000097:blood / Q000473:pathology; D006017:Glycolipids / Q000097:blood* / Q000302:isolation & purification; D006023:Glycoproteins / Q000097:blood* / Q000302:isolation & purification; D006801:Humans; D007983:Lewis Blood Group Antigens; D008970:Molecular Weight; D009367:Neoplasm Staging
D000911:Antibodies, Monoclonal; D000941:Antigens; D006017:Glycolipids; D006023:Glycoproteins; D007983:Lewis Blood Group Antigens